DEFECTIVE EXPRESSION OF GP180, A NOVEL CD8 LIGAND ON INTESTINAL EPITHELIAL-CELLS, IN INFLAMMATORY BOWEL-DISEASE

Previous studies support a role for intestinal epithelial cells (IEC) as antigen-presenting cells in mucosal immune responses, T cells activ ated by IEC are CD8+, suppressor in function, and dependent upon CD8-a ssociated D56lck activation, A 180-kD glycoprotein (gp180) recognized by mAbs B9 and L12 has been identified and shown to be important in CD 8+ T cell activation by IEC. Since IEC derived from patients with infl ammatory bowel disease (IBD) are incapable of activating CD8+ T cells, we asked whether this correlated with gp180 expression, While frozen sections of normal bowel revealed bright gp180 staining on all IEC, bo th inflamed and uninflamed ulcerative colitis (UC) specimens showed pa tchy staining, In Crohn's disease (CD), staining was faint to absent, Flow cytometry confirmed Immunohistochemical data, The staining patter ns correlated with the ability of IEC tb activate CD8-associated p56lc k. Normal IEC induced phosphorylation of p56lck in CD8 alpha but not C D4+ transfectants. In contrast, both UC and CD LEC activated CD4 and, to a much lesser extent, CD8-associated p56lck. Thus, gp180 expression by IBD IEC appears to be altered, and correlates with a functional al teration of lck activation, This defect may reflect a more proximal ev ent in the pathogenesis of IBD.